Expedient Synthesis and Antibacterial Activity of Tetrahydro-1′H-spiro[indoline-3,4′-quinoline]-3′-carbonitrile Derivatives Using Piperidine as Catalyst

Nangagoundan Vinoth; Pullar Vadivel; Appaswami Lalitha

doi:10.1055/s-0040-1706682

Synlett, Table of Contents

Synlett 2021; 32(07): 708-712
DOI: 10.1055/s-0040-1706682

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Expedient Synthesis and Antibacterial Activity of Tetrahydro-1′H-spiro[indoline-3,4′-quinoline]-3′-carbonitrile Derivatives Using Piperidine as Catalyst

Nangagoundan Vinoth

^aDepartment of Chemistry, Periyar University, Salem-636011, Tamilnadu, India

,

Pullar Vadivel

^bDepartment of Chemistry, Salem Sowdeswari College, Salem-636010, Tamilnadu, India

,

Appaswami Lalitha∗

^aDepartment of Chemistry, Periyar University, Salem-636011, Tamilnadu, India

› Author Affiliations

Abstract

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Abstract

A convenient synthesis of 2′-amino-7′,7′-dimethyl-2,5′-dioxo-1′-(phenylamino)-5′,6′,7′,8′-tetrahydro-1′H-spiro[indoline-3,4′-quinoline]-3′-carbonitrile derivatives has been designed using different substituted isatins, various 5,5-dimethyl-3-(2-phenylhydrazinyl)cyclohex-2-enones (arylhydrazones of dimedone) and malononitrile in ethanol with piperidine as catalyst at room temperature. The structures of the synthesized compounds have been elucidated by various spectroscopic techniques. The selected compounds have also been evaluated for their antibacterial activities against human pathogenic bacteria.

Key words

antibacterial activity - base catalysts - quinolines - indoline - multistep synthesis

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References

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42 Synthesis of Tetrahydro-1′H-spiro[indoline-3,4′-quinoline]-3′-carbonitrile Derivatives; General Procedure: All the chemicals used for this study were commercially available and were freshly used after being purified by standard procedures. All the conventional reactions were performed with 50 mL RB flasks. TLC was performed on Merck pre-coated aluminum sheets of 60 F-254 silica gel plates with visualization by UV-light using a 1:1 mixture of ethyl acetate and n-hexane as solvent system. Melting points were determined in capillary tubes with a Büchi melting point BB-545 apparatus and are uncorrected. ¹H and ¹³C NMR spectra were recorded with Bruker 400 MHz high-resolution NMR spectrometers. DMSO-d ₆ was used as a solvent for the NMR spectral measurements and the spectra were recorded in parts per million with TMS as internal standard. Spectral Data for Tetrahydro-1′H-spiro[indoline-3,4′-quinoline]-3′-carbonitrile Derivatives
2′-Amino-2,5′-dioxo-1′-(phenylamino)-5′,6′,7′,8′-tetrahydro-1′H-spiro[indoline-3,4′-quinoline]-3′-carbonitrile (6a): Yield: 87%; white solid; mp 230–232 °C. IR (KBr): 3413.80, 3261.14, 3030.31, 2952.89, 2184.18, 1717.19, 16630.76 cm^–1. ¹H NMR (400 MHz, DMSO-d ₆): δ = 10.22 (s, 1 H, -NH), 8.79 (s, 1 H, -NH), 7.38–6.42 (m, 11 H, Ar-H and –NH₂), 2.19–1.91 (m, 4 H, 2 × CH₂), 0.93–0.81 (m, 6 H, 2 × CH₃). ¹³C NMR (100 MHz, DMSO-d ₆): δ = 27.17, 28.67 (C(CH₃)₂), 31.17 (-CH), 38.36 (-CH₂), 49.60 (CH₂-CO), 58.74 (C-CN), 109.39, 110.73, 111.03, 120.79, 121.89, 122.02, 128.16, 130.10, 137.09, 142.15, 153.09, 179.82, 190.10 (Ar-C). 2′-Amino-6-methoxy-2,5′-dioxo-1′-(phenylamino)-5′,6′,7′,8′-tetrahydro-1′H-spiro[indoline-3,4′-quinoline]-3′-carbonitrile (6b): Yield: 80%; white solid; mp 226–228 °C; IR (KBr): 3429.77, 3248.56, 3030.35, 2957.27, 2186.55, 1723.40, 1650.66 cm^–1. ¹H NMR (400 MHz, DMSO-d ₆): δ = 10.05 (s, 1 H, -NH), 8.80 (s, 1 H, -NH), 7.35–6.43 (m, 10 H, Ar-H and –NH₂), 3.66 (s, 3 H, OCH₃), 2.19–1.93 (m, 4 H, 2 × CH₂), 0.93–0.74 (m, 6 H, 2 × CH₃). ¹³C NMR (100 MHz, DMSO-d ₆): δ = 27.13, 28.56 (C(CH₃)₂), 32.18 (-CH), 38.34 (-CH₂), 49.41 (CH₂-CO), 55.63 (-OCH₃), 58.80 (C-CN), 109.55, 111.02, 120.66, 129.89, 135.53, 147.25, 155.24, 179.67 (Ar-C). 2′-Amino-6-chloro-2,5′-dioxo-1′-(phenylamino)-5′,6′,7′,8′-tetrahydro-1′H-spiro[indoline-3,4′-quinoline]-3′-carbonitrile (6c): Yield: 76%; white solid; mp 230–232 °C; IR (KBr): 3327.35, 3096.69, 2958.88, 2876.92, 1722.43, 1691.16, 1644.67 cm^–1. ¹H NMR (400 MHz, DMSO-d ₆): δ = 10.99 (s, 1 H, -NH), 8.86 (s, 1 H, -NH), 7.44–6.65 (m, 10 H, Ar-H and –NH₂), 1.94–1.84 (m, 4 H, 2 × CH₂), 0.94–0.80 (m, 6 H, 2 × CH₃). ¹³C NMR (100 MHz, DMSO-d ₆): δ = 26. 44, 27.04, 28.73 (C(CH₃)₂), 33.68 (-CH₂), 50.63 (CH₂-CO), 59.10 (C-CN), 100.59, 108.51, 111.70, 112.99, 121.99, 126.89, 133.56, 144.76, 167.54, 180.32, 194.66, 203.54 (Ar-C). 2′-Amino-6-bromo-2,5′-dioxo-1′-(phenylamino)-5′,6′,7′,8′-tetrahydro-1′H-spiro[indoline-3,4′-quinoline]-3′-carbonitrile (6d): Yield: 79%; white solid; mp 232–234 °C; IR (KBr): 3422.48, 3246.68, 3029.36, 2954.58, 2186.34, 1724.50 cm^–1. ¹H NMR (400 MHz, DMSO-d ₆): δ = 10.04 (s, 1 H, -NH), 8.94 (s, 1 H, -NH), 7.50–6.58 (m, 9 H, Ar-H and –NH₂), 2.16–2.03 (m, 4 H, 2 × CH₂), 0.94–0.82 (m, 6 H, 2 × CH₃). ¹³C NMR (100 MHz, DMSO-d ₆): δ = 27.65, 28.01 (C(CH₃)₂), 38.18 (-CH₂), 110.26, 111.55, 113.53, 119.10, 125.91, 130.78, 139.35, 146.42, 155.81, 179.41, 194.33 (Ar-C). 2′-Amino-2,5′-dioxo-1′-(phenylamino)-6-(trifluoromethoxy)-5′,6′,7′,8′-tetrahydro-1′H-spiro[indoline-3,4′-quinoline]-3′-carbonitrile (6e): Yield: 83%; white solid; mp 230–232 °C; IR (KBr): 3477.11, 3361.15, 3210.53, 3111.86, 3026.47, 2959.66, 2185.02, 1707.70 cm^–1. ¹H NMR (400 MHz, DMSO-d ₆): δ = 10.45 (s, 1 H, -NH), 8.82 (s, 1 H, -NH), 7.33–6.56 (m, 10 H, Ar-H and –NH₂), 2.12–1.94 (m, 4 H, 2 × CH₂), 0.93–0.71 (m, 6 H, 2 × CH₃). ¹³C NMR (100 MHz, DMSO-d ₆): 26.84, 27.19, 28.51 (C(CH₃)₂), 38.34 (-CH₂), 49.44 (CH₂-CO), 57.80 (C-CN), 110.04, 111.97, 116.14, 119.15, 120.71, 121.29, 129.90, 138.52, 141.26, 146.82, 147.13, 155.88, 179.92, 194.26 (Ar-C). 2′-Amino-1′-((4-chlorophenyl)amino)-6-methoxy-2,5′-dioxo-5′,6′,7′,8′-tetrahydro-1′H-spiro[indoline-3,4′-quinoline]-3′-carbonitrile (6f): Yield: 85%; white solid; mp 224–226 °C; IR (KBr): 3414.56, 3273.42, 3032.56, 2953.14, 2185.96, 1717.59, 1632.96 cm^–1. ¹H NMR (400 MHz, DMSO-d ₆): δ = 10.66 (s, 1 H, -NH), 8.93 (s, 1 H, -NH), 7.39–6.47 (m, 9 H, Ar-H and –NH₂), 3.66 (s, 3 H, OCH₃), 2.10–1.95 (m, 4 H, 2 × CH₂), 0.94–0.77 (m, 6 H, 2 × CH₃). ¹³C NMR (100 MHz, DMSO-d ₆): δ = 27.30, 28.57 (C(CH₃)₂), 39.35 (-CH₂), 49.39 (CH₂-CO), 55.66 (-OCH₃), 58.89 (C-CN), 109.58, 110.30, 111.16, 119.30, 124.08, 129.68, 135.57, 138.28, 145.93, 152.71, 155.04, 179.63, 194.10 (Ar-C). 2′-Amino-1′-((4-chlorophenyl)amino)-7′,7′-dimethyl-2,5′-dioxo-5′,6′,7′,8′-tetrahydro-1′H-spiro[indoline-3,4′-quinoline]-3′-carbonitrile (6g): Yield: 88%; white solid; mp 218–220 °C; IR (KBr): 3835.27, 3740.79, 3647.38, 3588.71, 3415.87, 3274.02, 3022.86, 2955.53, 2365.09, 2187.03, 1717.43, 1633.23 cm^–1. ¹H NMR (400 MHz, DMSO-d ₆): δ = 10.23 (s, 1 H, -NH), 8.92 (s, 1 H, -NH), 7.43–6.48 (m, 10 H, Ar-H and –NH₂), 2.14–1.92 (m, 4 H, 2 × CH₂), 0.94–0.76 (m, 6 H, 2 × CH₃). ¹³C NMR (100 MHz, DMSO-d ₆): 27.27, 28.61 (C(CH₃)₂), 32.21, 38.31 (-CH₂), 48.98 (CH₂-CO), 58.88 (C-CN), 109.41, 110.86, 113.48, 122.04, 128.15, 129.69, 142.15, 145.93, 146.15, 152.68, 179.88 (Ar-C). 2′-Amino-1′-((4-bromophenyl)amino)-7′,7′-dimethyl-2,5′-dioxo-5′,6′,7′,8′-tetrahydro-1′H-spiro[indoline-3,4′-quinoline]-3′-carbonitrile (6h): Yield: 85%; white solid; mp 218–220 °C; IR (KBr): 3834.72, 3740.38, 3670.97, 3647.88, 3418.33, 3252.46, 2952.41, 2867.11, 2353.77, 2187.88, 1720.88 cm^–1. ¹H NMR (400 MHz, DMSO-d ₆): δ = 10.23 (s, 1 H, -NH), 8.93 (s, 1 H, -NH), 7.55–6.48 (m, 10 H, Ar-H and –NH₂), 2.14–1.92 (m, 4 H, 2 × CH₂), 0.94–0.77 (m, 6 H, 2 × CH₃). ¹³C NMR (100 MHz, DMSO-d ₆): δ = 27.24, 28.59 (C(CH₃)₂), 32.21, 38.31 (-CH₂), 48.98 (CH₂-CO), 58.88 (C-CN), 109.41, 110.83, 111.15, 111.68, 113.96, 119.30, 121.90, 122.05, 123.14, 128.16, 132.52, 136.98, 137.24, 142.14, 146.34, 152.65, 155.03, 179.77, 194.10 (Ar-C). 2′-Amino-1′-((4-bromophenyl)amino)-6-methoxy-7′,7′-dimethyl-2,5′-dioxo-5′,6′,7′,8′-tetrahydro-1′H-spiro[indoline-3,4′-quinoline]-3′-carbonitrile (6i): Yield: 77%; white solid; mp 222–224 °C; IR (KBr): 3414.69, 3275.63, 3034.04, 2953.82, 2185.81, 1717.55, 1678.20, 1633.28 cm^–1. ¹H NMR (400 MHz, DMSO-d ₆): δ = 10.06 (s, 1 H, -NH), 8.93 (s, 1 H, -NH), 7.51–6.47 (m, 9 H, Ar-H and –NH₂), 3.63 (s, 3 H, OCH₃), 2.15–1.95 (m, 4 H, 2 × CH₂), 1.08–0.84 (m, 6 H, 2 × CH₃). ¹³C NMR (100 MHz, DMSO-d ₆): δ = 27.28, 28.55 (C(CH₃)₂), 32.23, 49.39 (CH₂-CO), 55.67 (-OCH₃), 58.85 (C-CN), 109.58, 109.74, 110.33, 115.15, 112.39, 113.97, 132.50, 135.57, 138.28, 146.34, 152.68, 155.02, 179.63, 194.10 (Ar-C). 2′-Amino-6-chloro-1′-((4-chlorophenyl)amino)-7′,7′-dimethyl-2,5′-dioxo-5′,6′,7′,8′-tetrahydro-1′H-spiro[indoline-3,4′-quinoline]-3′-carbonitrile (6j): Yield: 79%; white solid; mp 232–234 °C; IR (KBr): 3914.60, 3790.02, 3702.05, 3423.01, 3249.96, 3030.35, 2956.62, 2355.64, 2186.71, 1723.46, 1654.28, 1630.26 cm^–1. ¹H NMR (400 MHz, DMSO-d ₆): δ = 10.39 (s, 1 H, -NH), 8.98 (s, 1 H, -NH), 7.39–6.58 (m, 9 H, Ar-H and –NH₂), 2.15–2.03 (m, 4 H, 2 × CH₂), 0.94–0.80 (m, 6 H, 2 × CH₃). ¹³C NMR (100 MHz, DMSO-d ₆): δ = 27.69, 28.07 (C(CH₃)₂), 32.31, 38.20 (-CH₂), 49.29 (CH₂-CO), 58.05 (C-CN), 110.22, 113.66, 123.20, 124.15, 125.79, 127.91, 128.08, 129.68, 138.96, 139.23, 141.30, 141.37, 145.89, 152.93, 153.13, 155.60, 179.52, 194.30 (Ar-C). 2′-Amino-1′-((4-bromophenyl)amino)-6-chloro-7′,7′-dimethyl-2,5′-dioxo-5′,6′,7′,8′-tetrahydro-1′H-spiro[indoline-3,4′-quinoline]-3′-carbonitrile (6k): Yield: 76%; white solid; mp 228–230 °C; IR (KBr): 3423.43, 3242.89, 2956.16, 2871.31, 2186.75, 1725.02, 1654.56, 1630.70 cm^–1. ¹H NMR (400 MHz, DMSO-d ₆): δ = 10.39 (s, 1 H, -NH), 8.94 (s, 1 H, -NH), 7.51–6.58 (m, 9 H, Ar-H and –NH₂), 2.15–2.03 (m, 4 H, 2 × CH₂), 0.94 (m, 6 H, 2 × CH₃). ¹³C NMR (100 MHz, DMSO-d ₆): δ = 27.65, 28.27 (C(CH₃)₂), 32.30, 38.19 (-CH₂), 49.29 (CH₂-CO), 58.02 (C-CN), 110.21, 111.73, 114.12, 123.20, 125.79, 127.92, 128.08, 132.50, 132.65, 138.94, 139.22, 141.29, 146.29, 152.90, 153.09, 155.57, 179.52, 194.31 (Ar-C).

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